ArticleCell death & disease2023
DNA methylation-activated full-length EMX1 facilitates metastasis through EMX1-EGFR-ERK axis in hepatocellular carcinoma.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- DNA Methylation-Guided Prediction and Validation of TAAD Molecular Targets.Biochemical genetics · 2026Article
- Association between serum perfluoroalkyl substances and COPD risk: population evidence and in vitro validation.BMC pulmonary medicine · 2026Article
- PSMC2 promotes hepatocellular carcinoma progression through interaction with EGFR.Clinical and experimental medicine · 2026Article
- Uttroside B, a US FDA-designated 'Orphan Drug', mitigates the development of hepatocellular carcinoma and its pulmonary metastasis via EGFR/ERK-mediated inhibition of SREBP-1 and STAT-3.Cell death discovery · 2026Article
- Cost-Effective Identification of Hepatocellular Carcinoma from Cirrhosis or Chronic Hepatitis Virus Infection Using Eight Methylated Plasma DNA Markers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Comprehensive review and updated analysis of DNA methylation in hepatocellular carcinoma: From basic research to clinical application.Clinical and translational medicine · 2024Review
- Epigenetic Modifiers in Cancer Metastasis.Biomolecules · 2024Review
- Mechanisms and therapeutic targets of ErbB family receptors in hepatocellular carcinoma: a narrative review.Translational cancer research · 2024Review
- Integration of gene expression and DNA methylation data using MLA-GNN for liver cancer biomarker mining.Frontiers in genetics · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Altered DNA methylation is a crucial epigenetic event in hepatocellular carcinoma (HCC) development and progression. Through methylation-transcriptomic analysis, we identified a set of sixty potential DNA methylation-based epidriver genes. In this set of genes, we focused on the hypermethylation of EMX1, which is frequently observed in hepatobiliary tumors. Despite of its frequent occurrence, the function of EMX1 remains largely unknown. By utilizing bisulfite-next-generation sequencing, we have detected EMX1 DNA hypermethylation on the gene body, which is positively correlated with EMX1 mRNA expression. Further analysis revealed that EMX1 mRNA terminal exon splicing in HCC generated two protein isoforms: EMX1 full length (EMX1-FL) and alternative terminal exon splicing isoform (EMX1-X1). Cellular functional assays demonstrated that gain-of-function EMX1-FL, but not EMX1-X1, induced HCC cells migration and invasion while silencing EMX1-FL inhibited HCC cells motility. This result was further validated by in vivo tumor metastasis models. Mechanistically, EMX1-FL bound to EGFR promoter, promoting EGFR transcription and activating EGFR-ERK signaling to trigger tumor metastasis. Therefore, EGFR may be a potential therapeutic target for EMX1-high expression HCC. Our work illuminated the crucial role of gene body hypermethylation-activated EMX1-FL in promoting tumorigenesis and metastasis in HCC. These findings pave the way for targeting the EMX1-EGFR axis in HCC tumorigenicity and metastasis.
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